title: Refining tumor-associated aneuploidy through 'genomic recoding' of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas.
abstract: Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. 'Genomic recoding' of canine NHL data into a 'virtual human' chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Thomas
authors.forename: Eric L
authors.initials: EL
authors.lastname: Seiser
authors.forename: Alison
authors.initials: A
authors.lastname: Motsinger-Reif
authors.forename: Luke
authors.initials: L
authors.lastname: Borst
authors.forename: Victor E
authors.initials: VE
authors.lastname: Valli
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kelley
authors.forename: Steven E
authors.initials: SE
authors.lastname: Suter
authors.forename: David
authors.initials: D
authors.lastname: Argyle
authors.forename: Kristine
authors.initials: K
authors.lastname: Burgess
authors.forename: Jerold
authors.initials: J
authors.lastname: Bell
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Modiano
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001947:Breeding; D055028:Comparative Genomic Hybridization; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D016130:Immunophenotyping; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16